The embodiments described herein relate generally to medical devices for therapeutic electrical energy delivery, and more particularly to the surgical specialty of urology. Specifically, systems and methods for delivering electrical energy in the context of ablating tissue rapidly and selectively in minimally invasive transurethral clinical therapies by the application of suitably timed pulsed voltages that generate irreversible electroporation of cell membranes. Such irreversible electroporation can possibly be generated in conjunction with the application of disclosed means of enhancing electroporation efficacy.
Transurethral resection of the prostate (TURP) remains the gold standard for treating benign prostatic hypertrophy (BPH). Alternatives to surgical resection are ablation of tissues using thermal-based destruction of tissue using multiple forms of energy (laser, microwave, radiofrequency ablation etc.). The most common postoperative complication with known transurethral procedures is urethral stricture, occurring in approximately 4.4% of patients overall. Furthermore known transurethral procedures indiscriminately resect or ablate urethral epithelium in the process of de-bulking the prostate tissues. The urethral injury contributes to the recovery time and morbidity of the acute procedure.
In the past decade or two the technique of electroporation has advanced from the laboratory to clinical applications, while the effects of brief pulses of high voltages and large electric fields on tissue has been investigated for the past forty years or more. It has been known that the application of brief high DC voltages to tissue, thereby generating locally high electric fields typically in the range of hundreds of Volts/centimeter can disrupt cell membranes by generating pores in the cell membrane. While the precise mechanism of this electrically-driven pore generation or electroporation is not well understood, it is thought that the application of relatively large electric fields generates instabilities in the lipid bilayers in cell membranes, causing the occurrence of a distribution of local gaps or pores in the membrane. If the applied electric field at the membrane is larger than a threshold value, the electroporation is irreversible and the pores remain open, permitting exchange of material across the membrane and leading to apoptosis or cell death. Subsequently the tissue heals in a natural process.
Historically, known direct current ablation techniques were pioneered in cardiovascular catheter-based ablation. More recently these techniques have been applied for the treatment of solid tumors with a clinical tool that employed very short impulses. The application of known ablation techniques to solid tumors on other applications, however, has not included selectively targeting tissue for irreversible electroporation ablation. Specifically, tissue susceptibility to irreversible cell injury from strong brief pulses of electricity depends on a number of important variables. Factors include: cell size, geometry, and orientation within the electric field, the constitution of the cell membrane and organelles, and local temperature. While pulsed DC voltages are known to drive electroporation under the right circumstances, the examples of electroporation applications in medicine and delivery methods described in the prior art do not discuss specificity and rapidity of action.
Thus, there is a need for selective energy delivery for electroporation and its modulation in various tissue types as well as pulses that permit rapid action and completion of therapy delivery. There is also a need for more effective generation of voltage pulses and control methods, as well as appropriate devices or tools addressing a variety of specific clinical applications, particularly in minimally invasive applications. Such more selective and effective electroporation delivery methods can broaden the areas of clinical application of electroporation including therapeutic treatment of a variety of cardiac arrhythmias, tissue ablation, and transurethral applications.